Centene Off-Label Drug Use Prior Auth Update

Coverage Criteria

Initial Therapy (Pharmacy)

Covered when ALL of the following are met:

Initial Pharmacy Off-Label Criteria: 1) There are no pharmacy and therapeutic committee approved off-label use criteria for the diagnosis; 2) If a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of that drug-specific clinical policy; 3) Use must be diagnosis-specific as defined by ICD-9 or ICD-10 code(s); 4) Use is supported by ONE of: (a) NCCN Drug Information and Biologics Compendium level 1, 2A, or 2B; (b) evidence from at least two high-quality published studies or evidence-based clinical practice guidelines meeting representativeness and design criteria; (c) Micromedex DrugDex with strength of recommendation Class I or IIa; (d) state pediatric supportive references when member age is beyond FDA labeling (see Appendix G); 5) Request is not for a benefit-excluded use (e.g., cosmetic); 6) Prescribed by or in consultation with an appropriate specialist for the diagnosis; 7) Failure of two formulary agents as described (preferred biosimilar used if available, or generics/alternatives per sequencing rules) tried at maximum indicated doses each for at least 30 days or an appropriate duration unless contraindicated or clinically significant adverse effects occur; (Illinois HIM step therapy exceptions apply per IL HB 5395 and state oncology/mental health exceptions per Appendices E and H); 8) If request is for a non-preferred biologic with an available biosimilar, member must use the preferred biosimilar product(s) unless contraindicated or clinically significant adverse effects are experienced (state oncology/mental health exceptions apply); 9) Member has no contraindications to the prescribed agent per the product information label; 10) If applicable, prescriber has taken necessary measures to minimize any risk associated with a boxed warning in the product information label; 11) Dosing regimen and duration are within dosing guidelines recommended by clinical practice guidelines and/or medical literature.

Approval duration: Duration of request or 6 months (whichever is less)

Initial Therapy (Medical)

Covered when ALL of the following are met:

Initial Medical Off-Label Criteria: 1) There are no pharmacy and therapeutic committee approved off-label use criteria for the diagnosis; 2) If a drug-specific clinical policy is available, the request is not for diagnoses or indications listed in Section III of that drug-specific clinical policy; 3) Use is supported by ONE of: (a) NCCN Drug Information and Biologics Compendium level 1, 2A, or 2B; (b) evidence from at least two high-quality published studies or evidence-based clinical practice guidelines meeting representativeness and design criteria; (c) Micromedex DrugDex with strength of recommendation Class I or IIa; (d) state pediatric supportive references when member age is beyond FDA labeling (see Appendix G); 4) Request is not for a benefit-excluded use (e.g., cosmetic); 5) Prescribed by or in consultation with an appropriate specialist for the diagnosis; 6) Failure of two alternative drugs as described (preferred biosimilar used if available, or generics/alternatives per sequencing rules) tried at maximum indicated doses unless contraindicated or clinically significant adverse effects occur (Illinois HIM step therapy exceptions apply per IL HB 5395 and state oncology/mental health exceptions per Appendices E and H); 7) If request is for a non-preferred biologic with an available biosimilar, member must use the preferred biosimilar product(s) unless contraindicated or clinically significant adverse effects are experienced (state exceptions apply); 8) Member has no contraindications to the prescribed agent per the product information label; 9) If applicable, prescriber has taken necessary measures to minimize any risk associated with a boxed warning in the product information label; 10) Dosing regimen and duration are within dosing guidelines recommended by clinical practice guidelines and/or medical literature.

Approval duration: Duration of request or 6 months (whichever is less)

Continued Therapy

Covered for continuation when ALL of the following are met:

Continued Therapy: 1) Member meets one of: (a) currently receiving medication via Centene benefit; (b) member has previously met initial approval criteria; or (c) state or health plan continuity of care programs apply with documentation that member has received this medication for at least 30 days (see CC.PHARM.03A/03B and state addendums) AND use is supported by ONE of: NCCN level 1, 2A, or 2B; at least two high-quality published studies or evidence-based guidelines meeting design criteria; Micromedex DrugDex Class I or IIa; or state pediatric supportive references when applicable; 2) Member is responding positively to therapy; 3) If request is for a non-preferred biologic with an available biosimilar, member must use the preferred biosimilar product(s) unless contraindicated or exceptions apply (state oncology/mental health exceptions per Appendices E and H; IL HIM exceptions per IL HB 5395); 4) If request is for a dose increase, member has been titrated from the lower dose with documentation of partial improvement and the new dose does not exceed dosing guidelines recommended by product label, clinical practice guidelines, and/or medical literature.

Approval duration: Duration of request or 12 months (whichever is less)

High-level coverage criteria

Covered when ALL of the following state- and benefit-specific conditions are met, per detailed criteria elsewhere in the policy:

Core requirements: Request includes clinical evidence per accepted methods (randomized controlled trials preferred; non-randomized trials acceptable in some cases per Appendix F), involves an appropriate specialist when required, documents trials/failures of formulary agents or appropriate alternatives when such agents exist, assesses contraindications and black box warnings, and complies with dosing limits and guideline-recommended regimens.

Summary references: policy revisions and appendices

Pediatric exception: If member age is beyond FDA labeling for pediatric use, submission must include state-accepted supportive references listed in Appendix G.

State-specific per Appendix G

Biosimilar requirement: For requests for a non-preferred biologic with an available biosimilar, the member must use the preferred biosimilar product(s) unless contraindicated or clinically significant adverse effects occur.

Applies at initial authorization; state exceptions and IL HIM considerations noted

The following indications or diagnoses are not eligible for coverage because the drug has been demonstrated to be unsafe or ineffective for those uses. Coverage is not authorized for any request that falls within these excluded indications or diagnoses.

Requests where the treatment is for a benefit-excluded use (e.g., cosmetic) are not eligible for coverage under the pharmacy benefit criteria and will not be approved.

Uses that are supported only by case reports (uncontrolled, anecdotal information) do not provide adequate supportive clinical evidence and are not sufficient to meet the policy’s evidentiary requirements for accepted off-label uses.

Initial Therapy

Top-level initial therapy coverage decision node. Includes mapping to pharmacy and medical criteria sets.

Pharmacy benefit mapping: Apply Initial Therapy (Pharmacy) criteria set.
Medical benefit mapping: Apply Initial Therapy (Medical) criteria set.

Denial trigger: If the applicable initial therapy criteria set is not fully met (including evidence, specialist requirement, trial/failure of formulary agents, contraindication assessment, and dosing limits), the prior authorization request will not be approved.

Continued Therapy

Top-level continued therapy coverage decision node. Applies to pharmacy and medical continuation requests.

Continued Therapy: Authorization for continuation requires that the Continued Therapy criteria set is met in full: member currently receiving drug via Centene, previously met initial criteria, or qualifies under state/plan continuity of care with documentation of >=30 days therapy; ongoing use supported by accepted evidence; member responding to therapy; biosimilar sequencing rules applied where applicable; dose increases require prior titration and documented partial improvement and must remain within recommended dosing.

Duration: If continued therapy criteria are met, approval duration is the duration of request or 12 months (whichever is less).

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required for Off‑Label Use

Prior authorization is required for off-label uses. Prescribers requesting PA approval for an off‑label indication must submit documentation that supports the requested use and meets the criteria in this policy. PA requests that do not meet the established off‑label criteria will not be approved.

Applies to pharmacy and medical benefit requests as specified in the policy.
Refer to CC.PHARM.03B for California exceptions.

Documentation Required

Required Documentation

Prescribers must submit supporting documentation (such as office chart notes, lab results, imaging, prior medication history, and other clinical information) demonstrating that the member meets ALL applicable approval criteria before a PA can be approved. The clinical pharmacist or delegated reviewer will consider the request only if the required documentation is provided.

Step Therapy and Biosimilar Sequencing

Requirement	Details / sequencing	Notes / exceptions
Step therapy (formulary failures)
Failure of two formulary agents that are FDA‑approved for the requested indication (or recognized standards of care) tried at maximum indicated doses, each used for at least 30 days or an appropriate duration of treatment unless contraindicated or adverse effects
Includes alternative sequencing rules: preferred biosimilar(s) must be used if available; both agents may be generics from different manufacturers; if only one generic exists, at least one additional recognized standard of care agent must be used; applies to pharmacy and medical benefit unless state exception applies

Coverage-label	Policy statement	State-specific guidance / bypasses
Do not apply step therapy
Step therapy requirements are not applied where prohibited by state law (e.g., stage 4/advanced/metastatic cancer per Appendix D) or other state regulations
Appendix D lists states where step therapy is prohibited for advanced/metastatic cancer; Appendix H and 4Q2024 revision added bypass to all redirections in States with mental health redirection prohibitions; IL HIM requests exempt from step therapy as of 1/1/2026 per IL HB 5395 (with limited biosimilar exception)

Biosimilar and Non-Preferred Biologic Rules

Billing Rule

Use preferred biosimilar before non‑preferred biologic

If a preferred biosimilar is available, the member must use the preferred biosimilar product(s) unless contraindicated or clinically significant adverse effects are documented; this sequencing applies to initial and continued authorizations unless state oncology/mental‑health exceptions apply.

For Illinois HIM requests the step therapy/biosimilar sequencing may not apply as of 1/1/2026 unless the biosimilar is FDA‑listed as interchangeable (chunk 6, 12).

Billing Rule

Non‑preferred biologic requires preferred biosimilar trial

When the request is for a non‑preferred biologic and an appropriate biosimilar is available, the member must use the preferred biosimilar product(s) as a condition of approval.

Background

Off-label drug use refers to prescribing an FDA‑approved medication for an indication, treatment regimen, or patient population that is not included in the FDA‑approved product labeling. Many off‑label uses may have clinical merit, but determinations for coverage are made on a case‑by‑case basis using the policy’s evidentiary standards and prescriber documentation requirements.

Definitions

inv-17: Off-label use — definition key/value

TermOff-label use

DefinitionUse of an FDA-approved drug for indications, treatment regimens, or patient populations not included in approved labeling.

ContextMany off-label uses are effective and well-documented; prescribers requesting prior authorization must submit specified documentation.

inv-18: Case reports — definition key/value about case reports being inadequate evidence

Evidence typeCase reports

CharacteristicGenerally uncontrolled and anecdotal information.

Policy stance

Revision History

2021-07-22policy_revision

Revised clinical trial requirements, added specialist requirement, added requirement for trial of two formulary FDA‑approved drugs when available, added assessment of contraindications/black box warnings, and added dosing limits; added Nevada to Appendix F; added medical-benefit criteria set and other clarifications including redirection bypass for cancer in certain states.

2022-07-28policy_addition

Added state-specific pediatric criteria allowing use beyond FDA‑approved ages with Appendix G references and clarified drug‑specific exclusions and pharmacy benefit drug‑failure options.

2022-12-21

OpenPayer

Clinical Policy: Off-Label Drug Use

Coverage Criteria

Initial Therapy

Continued Therapy

Provider Actions and Prior Authorization

Step Therapy and Biosimilar Sequencing

Biosimilar and Non-Preferred Biologic Rules

Background

Definitions

Revision History